The invention concerns a cardiac pacemaker and more particularly to a self-calibrating rate-adaptive cardiac pacemaker.
Rate-adaptive cardiac pacemakers wherein the stimulation rate is set in dependence on signals received from the body of the patient, and which reflect the physiological demand of the patient with regard to cardiac activity, have long been known and used in a clinical context. Various proposals have also been put forward for self-adaptation (auto-calibration) of such rate-adaptive cardiac pacemakers.
For example, WO 93/20889 proposes a dual-sensor arrangement with one circuit for detecting the minute volume, and an additional activity sensor where the stimulation rate is determined based on target rates, which can be derived for the individual sensors. In another example, U.S. Pat. No. 5,065,759 proposes a dual-sensor arrangement in which the QT-interval is detected and evaluated as a, xe2x80x98physiologically exactxe2x80x99, but slowly responding parameter, and wherein physical activity is detected and evaluated as a rapidly responding parameter.
In yet another example, EP 0 147 820 also discloses a rate-adaptive pacemaker in which one of the two sensors is used as a so-called closed-loop sensor, which detects signals from the heart-circulation regulating circuit for rate adaptation purposes, whereas a further sensor only provides a monitoring function. In this system, it is only when errors in rate adaptation are detected by way of the monitoring sensor that the closed-loop sensor is temporarily replaced by the monitoring sensor or the configuration of the sensor characteristic is re-calibrated.
Meanwhile, EP 0 498 533 A1 proposes a rate-adaptive pacemaker operating with two sensors, in which the upper rate limit is set utilizing hemodynamical monitoring. Various sensors are known for this function, including a sensor designed to detect changes in the impedance of the right ventricle.
Finally, in an unpublished German patent application No. P 198 04 843.2, a self-calibrating rate-adaptive pacemaker was proposed in which a closed-loop rate adaptation algorithm based on intraventricularly detected impedance signals was calibrated by means of an acceleration sensor.
Signals emanating from the sympathetic nerve in the context of the autonomous system for heart-circulation control, referred to as xe2x80x98sympatheticxe2x80x99 signals, primarily indicate the need for cardiac minute volume, and in the neural equilibrium of the sound heart-circulation system, find their antagonist in signals emanating from the vagus nerve, referred to as xe2x80x98vagalxe2x80x99 or xe2x80x98parasympatheticxe2x80x99 signals, which indicate the attainment of upper limits in terms of the efficiency of the cardiac minute volume. In contrast to sympathetic signals, vagal signals therefore have an inhibiting effect.
In the known rate-adaptive pacemakers the change in inotropy is measured and used as a measurement of the required cardiac minute volume, and thus the optimum stimulation rate. In this respect, a linear relationship is assumed between inotropy and heart rate, i.e., a rise in inotropy is immediately answered by a proportional rise in the stimulation rate. Measurement of the inotropy by way of the ventricular contraction dynamics (by means of unipolar impedance measurement) predominantly detects the sympathetic component of autonomous regulation. Vagal components, and their (generally inhibiting) effect on the heart rate, are in practice not detected and taken into consideration. This xe2x80x98purely sympatheticxe2x80x99 pacemaker consequently functionsxe2x80x94at least in relation to heart ratexe2x80x94in an analogous fashion to a patient with a low level of baroreceptor reflex sensitivity; the vagal tone is artificially reduced to zero or set to a constant value and the sympathetic tone alone has a controlling action. This sympathetic dominant system results in two disadvantages: 1) rapid heart rate adaptations, as are possible with vagal involvement in relation to the functioning heart, cannot be implemented by the pacemaker; and 2) the function of the vagus nerve for controlling the heart rate dynamics also does not have any effect. This means that long-term effects (for example general physical fatiguexe2x80x94so-called xe2x80x98burn-outxe2x80x99xe2x80x94, a harbinger of incipient heart insufficiency, etc.) remain substantially disregarded.
This means that the actual advantage of autonomous monitoring, namely sparing the inotropic reserves and thus protecting against primary cardiomyopathies or arrhythmias, are not utilized in an optimal fashion. As a consequence of disregarding the vagal contribution, the calculated stimulation rate is not physiologically correct in terms of its absolute level, even if fall and rise times may be correct. The result is that the myocardium may, under some circumstances, be overloaded or not adequately loaded.
Accordingly, a need exists for a cardiac pacemaker of the general kind set forth above, which is optimized from the physiological point of view, which operates in a reliably self-calibrating fashion, and which can be implemented without problems.
The present invention is directed to a self-calibrating rate-adaptive cardiac pacemaker, and more particularly to a self-calibrating rate-adaptive cardiac pacemaker comprising a first measuring and processing device for detecting a first, predominantly sympathetically influenced physiological parameter (Z(tm)) and for obtaining a rate control parameter (RCPp), which has a control input for controlling the functional dependency of the rate control parameter on the first physiological parameter, in particular a response factor and/or an upper limit rate; and a stimulator unit for producing and outputting stimulation pulses at a stimulation rate which is determined by the rate control parameter, characterized by a second measuring and processing device for detecting and evaluating a second, predominantly vagally influenced physiological parameter (AVI) and for outputting a calibration signal (Cal) which is dependent on the evaluation result, to the control input of the first measuring and processing device.
In one embodiment, the invention is directed to a pacemaker which operates with a suitable vagal control contribution, and which uses signals from two closed-loop sensors for rate control purposes and more specifically a sensor which hereinafter is referred to for the sake of brevity as the xe2x80x98sympatheticxe2x80x99 sensor and a sensor which is referred to as the xe2x80x98vagalxe2x80x99 sensor. The influence of the vagus is primarily felt in the electrical and mechanical activity of the atria, such as, for example, the atrial evoked stimulation response {AERxe2x80x94to be measured by a unipolar procedure), the atrial monophase action potential {MAPxe2x80x94to be measured by a bipolar procedure), the atrial refractory time, the intra-atrial impedance, and also the AV-transition time. Meanwhile, the influence of the sympathetic nerve is expressed primarily in the activity of the ventricle, and more particularly to the ventricularly evoked stimulation response {VER), the ventricular monophase action potential {MAP), the ventricular refractory time, the intra-ventricular impedance, and the QT-interval. In such an embodiment, the sensor for signals which are dominated by the sympathetic nerve is referred to as the xe2x80x98sympatheticxe2x80x99 sensor, and the sensor for signals dominated by the vagus nerve is referred to as the xe2x80x98vagalxe2x80x99 sensor. In such a system the sympathetic signals react to changes in the heart-circulation system more slowly (with a time constant of about cardiac cycles) than vagal signals (with a time constant of about one cardiac cycle) and therefore the sensor time characteristics are also correspondingly different.
In one alternative embodiment, the invention includes the ability to current control the stimulation frequency in a closed-loop stimulation (CLS) with reference to the signals from the xe2x80x98sympatheticxe2x80x99 sensor.
In another alternative embodiment, the relative changes in the sensor signal are converted, in accordance with the response amplification effect or the response factor (which represents a measurement of the sensor dynamics), into stimulation frequencies which are directly proportional thereto, or, alternatively, into absolute sensor values are converted by way of a characteristic curve into rate-control signals.
In yet another alternative embodiment, the vagal sensor is used for calibration of the sympathetic sensor or more particularly the sensor dynamics (response factor or rise in the sensor characteristic) and the rate range which can be covered in the current control situation. For example, if the rate adaptation algorithm, by means of the sympathetic sensor, provides for ascertaining stimulation rates which are dynamically excessive or which basically are above the efficiency of the heart-circulation system, i.e., outside the hemodynamically justified rate range; then the inhibiting influence of the vagal nervous system is utilized through the vagal sensor. If, on the other hand, the vagus tone is low, the response factor and upper limit rate are increased and the sympathetic nerve tone reduced, whereupon a rise in vagus tone is to be expected.
In still another embodiment of the invention, (irrespective of the above-mentioned assumption of the fundamental dominance of sympathetic or vagal components in given kinds of cardiac signals), the separation of sympathetic and vagal signal components in the available, complexly determined signals is of particular significance. In such an embodiment, one possible way of separating the vagal and sympathetic signals, which is advantageous in terms of measuring procedure and which is very close to the behaviour of a healthy heart-circulation system, is based on modulation of the two tones and analysis of the responses of a suitably selected effector utilizing the different time constants. Therefore, the stimulation rate is modulated around the adaptive rate. Rapid modulation of the stimulation frequency (specifically on a beat-to-beat basis) can produce a variation, which is also rapid, in the signals of the vagal sensor, which variation must in turn assume a given extent in the optimum efficiency range of the heart. In contrast, slow modulation (extending for example over 10 cardiac cycles) of the stimulation frequency entrains a variation in the sympathetic signals.
In still yet another embodiment, the invention uses the intra-ventricular impedance as the sympathetic signal for rate adaptation purposes and the natural AV-transition time as the vagal signal for calibration purposes. In such an embodiment, detecting and suitably evaluating the intra-ventricular impedance allows for the measurement of the inotropy (beat strength or force of the cardiac muscle) and calculating therefrom the stimulation rate. In such a case excessive stimulation rates may occur with a rising stress and an excessive response factor. The AV-transition timexe2x80x94which is basically reduced in length with physiologically appropriately rising rate valuesxe2x80x94reacts thereto with an unnatural increase in length. Conversely, the AV-transition time reacts to a rise in the stimulation frequency, which is too low in relation to the hemodynamic demand, with an unnatural reduction in length. If the above-mentioned unnatural behaviour in terms of the AV-transition time is detected, the response factor can be corrected. On the basis of such a calibration, it is possible for the upper MCLR limit (xe2x80x98maximum closed-loop ratexe2x80x99) for the sensor rate range to be dynamically established as, when the maximum physiological stimulation rate is exceeded, the above- described unnatural increase in length of the AV-transition time may be noted.
In still yet another embodiment, calibration both in respect of sensor dynamics and also the sensor rate range can be implemented on the basis of the modulation of the stimulation frequency. In such an embodiment, in the case of rapid modulation, the variation in the AV-time at excessive stimulation rates, in comparison with its variation in the case of physiological stimulation rates, is displaced towards longer AV-times. This applies both with respect to instantaneously excessive stimulation rates and also stimulation rates which are above the efficiency of the heart.
In still yet another embodiment, evaluation of the impedance measurements is effected in accordance with the known ResQ- or rise processes (SCHALDACH, Max: Electrotherapy of the Heart, 1st edition, Springer-Verlag, pages 114 ff) in a wide range, which includes the ROI-ranges which are usually set for individual patients. In such an embodiment, the sensing time pairs are pre-programmed in such a way that they contain the pair which is xe2x80x98optimumxe2x80x99 for the patient in question. Establishing this optimum pair does not require programming individually to the patient after the implantation procedure. Instead, such values are preferably stored in a read-only memory during the production of the pacemaker. In such an embodiment, impedance detection and evaluation can be effected at a spontaneous ventricular signal, but by virtue of the signal shape which in such a situation is often unfavourable and fluctuating, detection at an evoked signal (VER) is preferred in practice. The point of reference for the choice of the sensing time pair in such a case is the ventricular stimulus.
In still yet another embodiment, the invention is directed to a process capable of managing the cardiac pacemaker with a lower level of calibration. In such an embodiment, the process calculates a value of the integral of the impedance curve on the basis of a plurality of support locations, and rate adaptation is implemented on the basis of changes in that integral value; see for example, DE 196 09 382 A1 incorporated herein by reference.
In still yet another embodiment, the characteristic which determines the dependency of the stimulation rate on the impedance value, as the first essential operating parameter of the rate-determining apparatus, is not static but is optimized continuously or at given time intervals on the basis of the detection of the AV-time in the event of a modulated stimulation rate. In such an embodiment, the width of variation and particularly the ICLR, as a second essential parameter, is not known at the beginning of operation. Instead, at the beginning of such an operation, an estimated value is predetermined as a starting value for the upper and lower limit values of the width of variation, and this value is continuously optimized during operation.